This invention relates to a measurement method and a biosensor apparatus using a resonator, used for example for the tracking and state analysis of chemical reactions in the fields of biochemistry, medicine and food.
In a biosensor apparatus using a QCM in related art, as shown in FIG. 17, a sample solution 8 is brought into contact with a piezoelectric device such as a quartz resonator 7 mounted at the bottom of a cylindrical cell 15, and either the quartz resonator, which is a sensor, is oscillated at its fundamental harmonic resonant frequency and a frequency change is measured, or an impedance analyzer is used to measure the frequency of the fundamental harmonic resonance point (the point at which the impedance is at a minimum) continuously, and from this frequency change the quantity of a material adsorbed to the piezoelectric device surface is measured.
However, during this measurement, frequency fluctuations over a range of several hundred Hz with a substantially constant period have arisen.
The reason for this is thought to be that pressure waves caused by the displacement of the quartz resonator are reflected at the liquid surface, and when with a load acting on the quartz resonator a change in the shape of the liquid surface caused by vibration of the liquid surface occurs or a fall of the liquid surface caused by evaporation of the solution occurs, the load fluctuates (Martin, B. A.; Hager, H. E.: J. Appl. Phys. 1989, “Flow profile above a quartz crystal vibrating in liquid”).
Because of this, in measurement methods of related art using the fundamental harmonic of the resonator, it has been necessary to reduce pressure waves by disturbing the liquid surface by moving up and down and/or rotating a stirring rod inside the cell or by treating the cell so as to make the liquid surface concave. Also, when the amount of the sample solution is very small, because agitating it is impossible and furthermore the liquid surface becomes convex due to surface tension, it has been impossible to avoid the influence of the above-mentioned frequency fluctuation.